Selenium and the Thyroid Gland

More Good News for Clinicians

Anne Drutel; Françoise Archambeaud; Philippe Caron

Disclosures

Clin Endocrinol. 2013;78(2):155-164. 

In This Article

General Points

Synthesis of Specific Selenoproteins

Selenium is an indispensible trace mineral for humans because of its antioxidant and antiinflammatory properties. Selenium is present in specific selenoproteins as selenocysteine. Selenocysteine, which is essential for enzyme activity,[2] is considered to be the 21st amino acid because it is encoded by a UGA codon, which is normally a stop codon and is co-translationally incorporated into proteins by specific tRNA; that is, the ribosomes are directed to translate the stop codon as selenocysteine by a particular stem-loop mRNA structure that is located in the 3′-untranslated region. The stem-loop structure (selenocysteine insertion sequence [SECIS] element) forms part of complex including a binding protein (SBP2) and a specialized elongation factor (EFsec), which donates the selenocysteine tRNA to a vacant ribosomal site, transforming the stop codon into a selenocysteine codon.[3]

The Principal Selenoproteins and their Functions

The principal selenoproteins, including glutathione peroxidase (GPXs) (seven genes), thioredoxin reductases (TRs) (three genes) and deiodinases (three genes), are expressed in the thyroid gland in large quantities. The main function of glutathione peroxidases is to protect the body against damage caused by oxygen free radicals, with each enzyme having a specific location.[4,5] Thioredoxin reductases play an essential role in antioxidant processes but are also implicated in the regulation of certain transcription factors (NF-K β, Ref-1, P53) and in gene expression. Finally, there are three deiodinase isoforms (D1, D2, D3) and their localization and functions vary depending on the tissues where they are found in humans ( Table 1 ).[5]

Selenium Sources and Recommendations

Proteinaceous foods (meat, fish, shellfish, offal, eggs, cereals, etc.) are the richest in selenium, but bioavailability of the selenium they contain is variable, i.e. 20–50% for seafood against more than 80% for cereals or brewer's yeast. However, the selenium content of cereals is highly dependent on the selenium content of the soil where they are grown. The soils of most European countries have a low selenium content, which explains the mild to moderate selenium deficiencies observed in Europe compared to North America where the selenium content of the soils is high. Severe deficiencies causing myxoedematous cretinism are observed in large parts of Central Asia.

Standard plasma selenium concentrations range between 60 and 120 μg/l or 0·8 ± 0·36 μmol/l. Indeed, plasma selenium concentration is related to dietary selenium, whereas selenoprotein P reflects selenium stocks in the body and appears a better marker of selenium status.[6] It is not recommended to carry out plasma selenium assays in routine practice because true selenium deficiencies are rare and essentially related to severe undernourishment or to the daily ingestion of very low doses due to geographic location. However, plasma assays may be useful to screen for patients in whom supplementation should be undertaken with caution or even avoided. In a cancer prevention study, an increase in the risk of type 2 diabetes was reported in patients long-term treated (average of 7·7 years) with 200 μg of selenium per day (relative risk of 2·7 compared with placebo).[7] The diabetogenic effect mainly affected patients whose plasma selenium concentrations were in the upper third of the normal range.

Thus, daily dose recommendations vary from one country to another, i.e. 55 μg/day in the United States, 75 μg/day for men and 60 μg/day for women in England, 1 μg/kg/day in France. In any event, doses should not exceed 400 μg/day[8] and may require decreasing if the potentially harmful effects of selenium are confirmed metabolically.

Very little information is currently available on the chemical nature of selenium contained in food. Selenomethionine has been identified as a major component of certain cereals (wheat, soybeans), yeasts and meat. Inorganic selenium (sodium selenite, selenate) has been identified in drinking water in small amounts. It is also used in food supplements. The bioavailability of sodium selenite is excellent, and it is used directly for the synthesis of specific selenoproteins. Given that synthesis is highly regulated, the risk of acute intoxication is only associated with very high doses (1000 μg/day).[9] The clinical signs of intoxication are asthenia, gastrointestinal disorders such as diarrhoea, bronchial or skin irritation, or hair loss and nail discoloration. Conversely, selenomethionine is not directly available for the synthesis of specific selenoproteins but is nonspecifically incorporated into proteins, essentially selenoalbumin, depending on its source. Metabolism of these nonspecific selenoproteins releases selenium, which may then be used for the synthesis of specific selenoproteins.[10] Use of selenomethionine appears to be safer and devoid of direct toxicity, even at high doses.[11]

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